First detection of foot-and-mouth disease virus O/Ind-2001d in Vietnam.

In recent years, foot-and-mouth disease virus (FMDV) serotype O, topotype Middle East-South Asia (ME-SA), lineage Ind-2001d has spread from the Indian subcontinent to the Middle East, North Africa, and Southeast Asia. In the current report, we describe the first detection of this lineage in Vietnam in May, 2015 in Dak Nông province. Three subsequent outbreaks caused by genetically related viruses occurred between May-October, 2015 after which the virus was not detected in clinical outbreaks for at least 15 subsequent months. The observed outbreaks affected (in chronological order): cattle in Dak Nông province, pigs in Dak Lak province and Dak Nông province, and cattle in Ninh Thuan province. The clinical syndromes associated with these outbreaks were consistent with typical FMD in the affected species. Overall attack rate on affected premises was 0.85 in pigs and 0.93 in cattle over the course of the outbreak. Amongst 378 pigs at risk on affected premises, 85 pigs died during the outbreaks; there were no deaths among cattle. The manner in which FMDV/O/ME-SA/Ind-2001d was introduced into Vietnam remains undetermined; however, movement of live cattle is the suspected route. This incursion has substantial implications for epidemiology and control of FMD in Southeast Asia.

Patients with thrombolysed stroke in Vietnam have an excellent outcome: results from the Vietnam Thrombolysis Registry.

BACKGROUND AND PURPOSE: We present the early experience in thrombolysis in three major centers of Ho Chi Minh city, namely 115 People Hospital, Gia Dinh Hospital, and An Binh Hospital. METHODS: A prospective study of consecutive patients treated with intravenous tPA with a treatment protocol similar to that of the National Institute of Neurological Disorders and Stroke (NINDS) trial. National Institutes of Health Stroke Scale (NIHSS) scores on admission and Modified Rankin Scale (MRS) scores at 3 months were measured for all patients. Intracranial and systemic hemorrhagic complications were recorded. RESULT: A total of 121 of 6171 (2%) patients with acute IS received thrombolysis over 3 years. Mean age was 57 years (range 18-78) and initial median NIHSS score was 12 (range 5-23). The mean delay between symptom onset and treatment was 143 min (range 50-210). Seventy-three (60.3%) patients received the standard dose with the remaining 48 patients (36.9%) treated with a lower dose, a mean calculated dose of 0.62 mg/kg (range, 0.6-0.86 mg/kg). Over half (56.3%) of the patients receiving low dose achieved functional independence (mRS score 0-1) at 3 months compared with 34.2% in the standard-dose group (P = 0.01). The 3-month mortality rate was also higher in the standard-dose group (2.1% vs. 12.5% with standard-dose tPA; P = 0.04). Symptomatic intracranial hemorrhage was noted in four patients of standard-dose group and one patient of low-dose group (P = 0.36). CONCLUSION: Intravenous thrombolysis, particularly in a lower dose, is safe and feasible in the treatment of acute IS in our selected Vietnamese population.

Thrombolysis in recurrent lacunar stroke: a case example.

BACKGROUND AND PURPOSE: We report a case of intravenous thrombolysis in a patient with early recurrent stroke. A 62-year-old man recovered nearly completely after a lacunar infarct of the left putamen. He suffered stroke recurrence 7 days later due to a new infarct in the left internal capsule. Intravenous alteplase 0.9 mg/kg was administered 40 min after the symptom onset resulting in significant neurologic improvement. CONCLUSION: Intravenous thrombolysis may be safe for early recurrent lacunar stroke in patients with relatively small risk of hemorrhage.

Human blood dendritic cells from allergic subjects have impaired capacity to produce interferon-alpha via Toll-like receptor 9.

BACKGROUND: High-affinity IgE receptor (Fc epsilon RI) expression on blood dendritic cells reportedly correlates with serum IgE levels. Our studies demonstrate that plasmacytoid dendritic cells (pDCs) secrete pro-inflammatory cytokines (IL-6, TNF-alpha) following Fc epsilon RI stimulation - a mode of activation that simultaneously reduces expression of Toll-like receptor 9 (TLR9). Whether or not TLR9 and/or Fc epsilon RI levels and their function on dendritic cells relate to allergic status is unknown. OBJECTIVE: The aim of this study is to compare the innate (TLR9-mediated) immune response of human pDCs to TLR9 and Fc epsilon RI alpha receptor expression in allergic and non-allergic subjects. METHODS: Basophil-depleted mononuclear cell fractions containing pDCs were prepared from peripheral blood of allergic and non-allergic subjects. Intracellular TLR9 and surface Fc epsilon RI alpha expression in blood dendritic cell antigen-2-positive cells were determined by flow cytometry. Activating anti-IgE antibody, anti-Fc epsilon RI alpha antibody, and TLR9 agonist were used to stimulate cell suspensions, with cytokine levels determined by ELISA. RESULTS: No difference in the frequency of pDCs was detected among allergic (n=9) vs. non-allergic (n=11) subjects (P=0.261). While there was also no difference in the baseline expression of TLR9, pDCs from allergic subjects produced sixfold less IFN-alpha when stimulated with CpG (P=0.002). Conversely, there was higher Fc epsilon RI alpha expression (P=0.01) on the pDCs of allergic subjects. CONCLUSIONS: Impaired TLR9-dependent immune responses in human pDCs are associated with allergic status and inversely correlated with Fc epsilon RI alpha expression. This impaired innate immune response among dendritic cells of allergic subjects may lead to more targeted therapeutic approaches and could provide a better understanding of the mechanisms underlying conventional and CpG-based immunotherapy.

Cotton wool plaques in non-familial late-onset Alzheimer disease.

Cotton wool plaques (CWP) are large, ball-like plaques lacking dense amyloid cores that displace adjacent structures. They were first described in a Finnish kindred with early-onset Alzheimer disease (AD) with spastic paraparesis due to a presenilin-1 delta9 mutation. We describe a case of sporadic late-onset AD with numerous neocortical CWP as well as severe amyloid angiopathy and marked leukoencephalopathy, compared with 16 cases of late-onset AD with similar degrees of amyloid angiopathy and leukoencephalopathy. The cases were studied with histologic methods and with single and double immunostaining for beta-amyloid (Abeta), paired helical filaments-tau (PHF-tau), neurofilament (NF), glial fibrillary acidic protein (GFAP), HLA-DR, and amyloid precursor protein (APP). We found that CWP were well-circumscribed amyloid deposits infiltrated by ramified microglia and surrounded by dystrophic neurites that were immunopositive for APP, but only weakly for NF and PHF-tau. Abeta1-12 was diffuse throughout the CWP, while Abeta37-42 was peripherally located and Abeta20-40 more centrally located. Two of the 16 late-onset AD cases also had CWP, but they were also admixed with diffuse plaques and plaques with dense amyloid cores. Pyramidal tract degeneration was not a consistent finding or a prominent feature in any case. The results suggest that CWP are not specific for early-onset familial AD with spastic paraparesis.

Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy.

Two extended haplotypes of the tau gene (H1 and H2) have been described. The frequency of H1 haplotype is increased in progressive supranuclear palsy (PSP). PSP is associated with filamentous tau lesions in neurons and glia, which are reportedly composed exclusively of tau isoforms with four repeats in the microtubule-binding domain (4R tau). To determine the influence of the tau haplotype on tau isoform composition and neuropathology, we studied 25 PSP cases and 6 Alzheimer's disease patients matched for age, sex, and postmortem delay. In the basal ganglia, tau and amyloid burdens were determined to see if there was an effect of concurrent Alzheimer-type pathology, and the ratio of 4R to 3R tau was measured in detergent-insoluble tau fractions. Insoluble tau from PSP was not composed exclusively of 4R tau. All brains had a mixture of 4R and 3R tau, but the ratio was different in Alzheimer's disease and PSP. In Alzheimer's disease there was less 4R than 3R tau, whereas the ratio was reversed in PSP. In PSP cases with concurrent Alzheimer-type pathology, the ratio of 4R to 3R was intermediate between Alzheimer's disease and PSP. The H1 haplotype had no effect on the 4R to 3R ratio or on tau and amyloid burdens. In summary, the H1 haplotype does not have a major influence on the pathological or biochemical phenotype of PSP.

A randomized, placebo-controlled trial of granulocyte colony-stimulating factor administration to newborn infants with neutropenia and clinical signs of early-onset sepsis.

OBJECTIVE: To determine whether recombinant human granulocyte colony-stimulating factor (G-CSF) administration: 1) accelerates production of neutrophils; 2) increases bone marrow stored and precursor neutrophils; and 3) is safe in newborn infants with neutropenia and clinical signs of early-onset sepsis. STUDY DESIGN: We randomized 20 infants with neutropenia and clinical signs of early-onset sepsis in the first 3 days of life to receive G-CSF (10 microg/kg/d) or placebo for 3 days. Entry criteria included neutropenia as defined by Manroe criteria, an elevated immature to total neutrophil ratio [(I/T) >/=0.25], and a requirement for ventilatory support. Cultures were obtained and antibiotics initiated on all study infants. Circulating absolute neutrophil count (ANC), I/T ratio, bone marrow neutrophil storage pool (NSP) and neutrophil proliferative pool (NPP), and plasma G-CSF concentrations were evaluated. Also, severity of illness as determined using the Score for Neonatal Acute Physiology (SNAP), morbidity, and mortality were recorded. RESULTS: Circulating ANC increased in both G-CSF and placebo recipients by day 1. Also, the I/T neutrophil ratio decreased in both G-CSF and placebo recipients. There were no significant differences in the ANC or I/T ratio between the two groups during the study period. Similarly, bone marrow NSP and NPP did not differ between G-CSF and placebo recipients at study entry or day 2. No differences were observed in the secondary outcome measures including severity of illness, morbidity, and mortality. CONCLUSIONS: Administration of recombinant G-CSF to infants with neutropenia and clinical signs of early-onset sepsis did not increase circulating ANC, or bone marrow NSP and NPP compared with placebo. No differences were observed between G-CSF and placebo recipients in severity of illness, morbidity, or mortality. No adverse effects of G-CSF administrations were noted.

Specific aspartic acid-rich sequences are responsible for silver staining of nucleolar proteins.

Ag-NOR proteins are silver-stainable proteins in the nucleolar organizer regions and are used to distinguish benign from malignant tumors. B23 and C23 are the two major Ag-NOR proteins. This study shows that only one of the two acidic clusters of B23 is responsible for its silver staining property. Fusion of this region of B23 (amino acids 161-188) to glutathione S-transferase produced an Ag-NOR positive fusion protein. The same result was obtained when amino acids 233-277 of C23 was fused with glutathione S-transferase. The aspartate residues, but not the glutamate residues, were found to be primarily responsible for the silver staining of the acidic clusters.

Comparison of bone mineral density in both hips.

Dual-photon absorptiometry (DPA) was performed on both hips of 40 patients to determine if the calculated bone-mineral density (BMD) of one hip could be used to predict the BMD of the opposite hip. For the Ward triangle, femoral neck, and greater trochanter the correlation coefficients between the BMD of the two hips was .920, .917, and .843, and the standard errors (SE) of the estimate for the linear regression of the left hip on to the right were 0.067, 0.063, and 0.077 g cm-2. The absolute error of predicting one hip from the other was not a function of BMD and thus the relative error increases with lower BMD values. The relative errors were 17%, 8%, and 7% for BMDs of 0.4, 0.8, and 1.0 g cm-2, respectively. The interobserver variability was small, with an r value of .96 and an SE of the estimate value of 0.036 g cm-2. The relative error in the mild-to-moderate osteoporosis categories was 2.5 times the precision of the instrument, indicating that the asymmetry of BMD is due to real differences between hips. Therefore the BMD of one hip cannot be used to predict that of the other with sufficient accuracy to discriminate clinically relevant trends in BMD.

99mTc-glucoheptonate for quantitation of differential renal function.

Differential renal function was calculated by using 99mTc-glucoheptonate (Tc-GH) in 51 patients. Computer-acquired background-corrected individual renal function was calculated by using both the 1-3-min uptake counts and the 2-4-hr delayed static counts. The degree of correlation between the two was high (r = .96). An equally high correlation was noted in 16 children who were 12 years old or younger, in 15 patients with renal size disparity greater than 60/40%, and in six patients with abnormal creatinine clearances. Ten patients had a 30-min dynamic 99mTc-DTPA study followed immediately by the injection of Tc-GH and acquisition of delayed static images 2-4 hr later. A high degree of correlation (r = .99) was seen between the 1-3-min differential function obtained by using Tc-DTPA and the 2-4-hr delayed differential function obtained by using Tc-GH. This study shows that Tc-GH is a clinically useful and valid tool for calculation of differential renal function and that Tc-GH combines many of the best aspects of Tc-DTPA and Tc-DMSA.

Oral colonization and susceptibility testing of Pseudomonas aeruginosa oral isolates from cystic fibrosis patients.

Microbial samples from the oral cavities of cystic fibrosis (C.F.) patients and 20 age-matched normal control subjects were characterized. Mucoid variant Pseudomonas aeruginosa was isolated from the tongue, buccal mucosa, and saliva of C.F. patients only. Analysis of the data suggests that the oral cavity is a potential reservoir for this organism. Aspiration and cross-contamination from this reservoir may be important in perpetuating chronic pulmonary infection in C.F. patients. Susceptibility testing was performed on 20 mucoid variant P. aeruginosa oral isolates obtained from the patients according to standardized broth dilution procedures. The in vitro antimicrobial effects of sodium fluoride, stannous fluoride, and chlorhexidine were measured. Analysis of the data suggests that clinically safe and achievable levels of chlorhexidine and stannous fluoride may be antimicrobial.